MONOCYTE SUPEROXIDE PRODUCTION IS INVERSELY RELATED TO NORMAL CONTENTOF ALPHA-TOCOPHEROL IN LOW-DENSITY-LIPOPROTEIN

Vitamin E (alpha-tocopherol) is a potent peroxyl radical scavenger. Ac cording to the oxidative theory of atherosclerosis, it prevents oxidat ion of low-density lipoprotein (LDL) and thereby lowers the risk of ca rdiovascular disease. It also mediates cell actions, and specifically decreases monocyte superoxide anion-production (O-2(.-)-production), w hich is involved in LDL oxidation. We investigated whether alpha-tocop herol-containing LDL decreases this production in a manner dependent o n the LDL alpha-tocopherol content (the alpha-tocopherol/apoB molar ra tio) in human, phorbol ester-stimulated, adherent monocytes. We found that O-2(.-)-production was inhibited by native LDL (n-LDL) in a manne r highly sensitive to the increasing alpha-tocopherol content (range 4 .5-8). In addition: (1) inhibition was greater when alpha-tocopherol w as associated to acetylated LDL (ac-LDL), the maximal percentage of in hibition being 80% as opposed to 35% for n-LDL; (2) the alpha-tocopher ol overloading of either form of LDL did not produce further inhibitio n; (3) the free form of alpha-tocopherol produced lower inhibition com pared with the lipoprotein-associated forms; (4) inhibition was not re lated to the cell content of alpha-tocopherol. We propose that the cel l targeting of alpha-tocopherol is crucial to the inhibition of monocy te O-2(.-)-production, and thus that the role of normal LDL-alpha-toco pherol contents (range 6-8) in the prevention of atherogenic processes needs to be reexamined. (C) 1998 Elsevier Science Ireland Ltd. All ri ghts reserved.